Aberrant expression of microRNA-26b and its prognostic potential in human cervical cancer

Background: microRNA-26b (miR-26b) is reported to be downregulated in many human malignancies and function as a tumor suppressor. However, the roles of miR-26b expression in cervical cancer progression are unclear. The aim of this study was to investigate the clinicopathological or prognostic significance of miR-26b in human cervical cancer. Methods: A cohort of 88 paired of cervical cancer and the adjacent normal cervical epithelial tissues were collected. Quantitative RT-PCR (qRT-PCR) assay was used to detect the expression of miR-26b and its correlations with clinicopathological factors were statistically analyzed. Finally, the survival was assessed by the Kaplan-Meier method and proportional hazards model. Results: The expression level of miR-26b in cervical cancer tissues was significantly lower than that in the adjacent normal cervical tissues (P<0.001). Reduced miR-26b was observed to be significantly correlated with advanced FIGO stage, higher incidence of lymph node metastasis and recurrence of cervical cancer patients (P=0.002, 0.036 and 0.029, respectively). In addition, patients with low-miR-26b expression showed poorer recurrence-free survival (RFS) and overall survival (OS) than those with high-miR-26b expression (P=0.0043 and 0.0015, respectively). Furthermore, multivariate analyses demonstrated that low miR-26b expression was an independent prognostic factor for predicting the 5-year RFS and OS of cervical cancer patients (P=0.013 and 0.007, respectively). Conclusion: Our results showed that reduced miR-26b was correlated with tumor development and poor prognosis in human cervical cancer. The status of miR-26b expression may be a potential prognostic biomarker for cervical cancer patients.     

Down-regulation of microRNA-124 is correlated with tumor metastasis and poor prognosis in patients with lung cancer

Introduction: MicroRNA-124 (miR-124) has been proven dysregulated in several human malignancies and correlated with tumor progression. However, its expression and clinical significance in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to investigate the clinical significance of miR-124 expression in NSCLC. Methods: Expression levels of miR-124 in 92 pairs of NSCLC and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: miR-124 expression level was significantly lower in NSCLC tissues compared with adjacent non-tumor tissues (P < 0.05). The 5-year OS of low miR-124 expression group was significantly shorter than that of high miR-124 expression group (P < 0.05). Moreover, the 5-year DFS of low miR-124 expression group was also significantly shorter than that of high miR-124 expression group (P < 0.05). In a multivariate Cox model, we found that miR-124 expression was an independent prognostic factor for both 5-year OS and 5-year DFS in NSCLC (P < 0.05). Conclusions: Our results offer the convincing evidence that miR-124 may play key roles in the progression of lung cancer and that the down-regulated expression of miR-124 may be independently associated with shorter OS and DFS of patients, suggesting that miR-124 might be a potential marker for further risk stratification in the treatment of lung cancer.     

Up-regulation of miR-335 predicts a favorable prognosis in esophageal squamous cell carcinoma

Introduction: MicroRNAs (miRNAs) are noncoding RNAs that regulate multiple cellular processes during cancer progression. MiR-335 has recently been identified to be involved in tumorigenesis of several cancers such as ovarian cancer and gastric cancer. However, the regulation of miR-335 in esophageal squamous cell carcinoma (ESCC) has not been reported yet. Methods: Expression of miR-335 in tumor and their normal matched tissues was determined by quantitative real-time PCR in 67 ESCC patients and its association with overall survival of patients was analyzed by statistical analysis. Results: The expression level of miR-335 was reduced in malignant tissue samples in comparison to normal matched tissue (P < 0.05). It was also proved that miR-335 expression was associated with ESCC histological grade, lymph node metastasis, tumor stage and clinical stage (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that low miR-335 expression was associated with poor prognosis in ESCC patients. Multivariate analysis showed that miR-335 expression was an independent prognostic marker of overall survival of ESCC patients. Conclusions: The study proves for the first time that miR-335 is down regulated in a majority of ESCC patients. Our results indicate that miR-335 expression is an independent prognostic factor for patients with esophageal cancer, which might be a potential valuable biomarker for ESCC.     

Loss of expression of EphB1 protein in serous carcinoma of ovary associated with metastasis and poor survival

Aberrant expression of receptors tyrosine kinase of Eph gene in human cancers is extensively documented. We previously found that EphB1 subtype is down-regulated in gastric cancer and colorectal cancer. Fore the more, decreased expression of EphB1 is related to invasion and metastasis in cancers. There is no published data regarding the role of EphB1 in ovarian cancer, which is the focus of the present study. The expression of EphB1 protein was determined in tissues from 74 patients with serous ovarian carcinoma and 12 normal ovarian epithelial tissues. The expression level of EphB1 protein in serous ovarian carcinoma was analyzed with respect to clinicopathological parameters and survival. EphB1 protein was positively stained in 12 normal ovarian epithelial samples, and negatively stained in 32 out of 74 (43.2%) serous ovarian cancers. Loss of expression of EphB1 protein was associated with higher tumor grade (P = 0.006), metastasis (P = 0.049) and high proliferative index Ki67 expression (P = 0.022), but not with FIGO stage (P = 0.0937), age at diagnosis (P = 0.624), and diameter of carcinoma (P = 0.108). In addition, loss of EphB1 protein in serous ovarian carcinoma was associated with a significantly worse overall survival (P = 0.015). Our data indicate that loss of EphB1 protein is associated with metastasis and poorer survival in patients with serous ovarian cancer. EphB1 may be used as a prognostic marker and a therapeutic target in serous ovarian carcinoma.     

MicroRNA-148b is down-regulated in non-small cell lung cancer and associated with poor survival

Background: The aim of this study was to clarify the clinicopathological significance of miRNA-148b (miR-148b) expression in NSCLC, and to explore the correlation between miR-148b level and the prognosis of patients with NSCLC. Methods: 151 patients diagnosed with NSCLC between May 2007 and April 2012 were included in the present study. Real-time RT-PCR method was used to assess the expression levels of miR-148b. The differences between two groups were assessed using Student’s t -test, and the Kaplan-Meier method was used to estimate overall survival. Results: The expression of miR-148b was decreased in tumor tissues compared to corresponding adjacent normal lung tissues (0.37 ± 0.12 vs. 1.00 ± 0.53, P < 0.05). Low miR-148b expression was significantly associated with TNM stage (P = 0.014), lymph node metastasis (P = 0.031), and distant metastasis (P = 0.008). Kaplan-Meier survival analysis showed that patients with low expression of miR-148b had significantly worse overall survival rates compared with those who had cancers with high miR-148b expression (log-rank test P = 0.039). Furthermore, multivariate Cox proportional hazards model analysis showed that miR-148b expression was independently associated with overall survival of patients with NSCLC (HR = 2.357, 95% CI: 1.612-9.212, P = 0.011). Conclusion: our data indicate that decreased expression of miR-148b in NSCLC tissues has prognostic value.     

Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival

Introduction: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. Methods: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. Results: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). Conclusions: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.     

Increased expression of miRNA-182 in colorectal carcinoma: an independent and tissue-specific prognostic factor

Increasing evidence has revealed that miRNAs play a pivotal role in multiple processes of carcinogenesis, and are being explored as diagnostic, prognostic and predictive biomarker. In this study, we investigated the status of miR-182 expression in colorectal carcinoma (CRC) by in situ hybridization and its underlying clinicopathologic significance for patients with CRC. We found that 79/138 (57.25%) CRCs had high-level expression of miR-182, while 17/67 (25.37%) normal mucosa tissues had high-level expression of miR-182. The expression level of miR-182 was remarkably up-regulated in CRC tissues compared with non-neoplastic normal tissues (P < 0.001). The over-expression of miR-182 in cancer parenchyma cells in CRC were strongly correlated with T-stage (P = 0.020), lymph node metastasis (P = 0.003), distant metastasis (P = 0.002), and Dukes’ stage (P = 0.005) in patients with CRC. Patients with high-level expression of miR-182 had short overall survival time than those with low-level expression of miR-182 (P < 0.001). Univariate and multivariate survival analyses further showed that miR-182 expression was a potential unfavorable prognostic factor for CRC, suggesting a potential application of miR-182 in prognosis prediction and therapeutic application in CRC.     

Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma

It has been well accepted that p53 overexpression is associated with advanced stages of cancer. However, the prognostic role of p53 overexpression in esophageal squamous cell carcinoma (ESCC) remains unclear. To investigate the prognostic role of p53 overexpression in patients with ESCC, a retrospective cohort study of 136 ESCC patients was carried out. The expression of p53 protein in tumor tissues was investigated immunohistochemically. Positive expression of p53 protein was detected in 57 ESCC patients (41.9%). The p53 overexpression was associated with smoking (P < 0.001), tumor differentiation (P < 0.001), and tumor size (P < 0.001). In the Kaplan-Meier analysis, patients with p53 overexpression had significantly shorter overall survival than those patients with negative p53 expression (log-rank P < 0.001). Multivariable analysis by Cox regression model further showed that p53 overexpression was a significantly independent predictor of poorer overall survival (hazard ratio [HR] = 1.91; 95% confidence interval [95% CI] 1.03-3.54, P = 0.04). Thus, p53 overexpression is associated with poor prognosis in patients with early stage esophageal squamous cell carcinoma, and it’s a significantly independent predictor of poorer overall survival.     

Up-regulation of miR-630 in clear cell renal cell carcinoma is associated with lower overall survival

Introduction: MicroRNAs (miRNAs) are noncoding RNAs that regulate multiple cellular processes during cancer progression. MiR-630 has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer and gastric cancer. However, the regulation of miR-630 in clear cell renal cell carcinoma (ccRCC) has not yet been reported before. Methods: Expression of miR-630 was evaluated by quantitative real-time PCR in tumour and their normal matched tissues in n = 92 ccRCC patients, and its association with overall survival of patients was analyzed by statistical analysis. Results: The expression level of miR-630 was significantly higher in renal cancer in comparison to normal matched tissue (P < 0.05). It is also proved that miR-630 expression was to be associated with renal cancer histologic grade, lymphnode metastasis, distant metastasis (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that high miR-630 expression was associated with poor prognosis in ccRCC patients. miR-630 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis. Conclusions: The study proves for the first time that miR-630 is upregulated in a majority of ccRCC patients. It also shows that miR-630 expression is an independent prognostic factor for patients with renal cancer, which might be a potential valuable biomarker for ccRCC.     

MicroRNA-153 expression and prognosis in non-small cell lung cancer

Background: miR-153 has been found to be significantly decreased in non-small cell lung cancer (NSCLC) tissues; however, its clinical significance has not been investigated. Methods: The expression patterns of miR-153 in 137 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed using qRT-PCR. The relationships between miR-153 expression and clinicopathological parameters were examined by chi-square test. Kaplan-Meier method and the log-rank test were used to determine the difference in overall survival (OS) rates between two groups. Results: The expression of miR-153 was reduced significantly, compared with adjacent normal lung tissues (P<0.05). We observed that the expression level of miR-153 was positively correlated with the clinical stage (P=0.005), lymph node status (P=0.014), distant metastasis (P=0.004), and differentiated degree (P<0.001) in NSCLC patients. According to the Kaplan-Meier survival analysis, the patients with low miR-153 expression exhibited evidently poorer overall survival rates than those with high miR-153 expression (P=0.003). Multivariate analysis showed that the expression of miR-153 was an independent and significant factor associated with poor OS rates (P=0.002). Conclusion: Decreased expression of miR-153 might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.     

Stomatin-like protein 2 expression is associated with clinical survival in patients with cervical cancer

Aims: To investigate the prognostic role of stomatin-like protein 2 (STOML2) in cervical cancer. Methods: The expression of STOML2 in 8 pairs of cervical cancer and adjacent normal cervical tissues were detected by Real-time PCR. Immunohistochemistry was performed to evaluation of STOML2 expression in 94 paraffin-embedded cervical cancer samples. The correlation between STOML2 expression and cervical cancer progression and prognosis was analyzed statistically. Results: STOML2 expression was upregulated in cervical cancer tissues compared with adjacent normal cervical tissues. Of the 94 cervical cancer cases, high STOML2 expression was detected in 54 cases (57.4%). STOML2 expression was significantly related to tumor stage (P = 0.013) and tumor size (P = 0.025). Moreover, patients with high expression of STOML2 had a significant shorter overall survival and recurrent free survival time compared with those with low STOML2 expression in cervical cancer (P = 0.001 and P = 0.017, respectively). Multivariate analysis revealed that STOML2 was an independent prognostic factor (P = 0.022) for the overall survival in cervical cancer. Conclusion: Our study showed STOML2 was correlated to progression in cervical cancer, and implicated it as a potential predictive factor for the prognosis of cervical cancer.     

Down-regulation of miR-503 expression predicate advanced mythological features and poor prognosis in patients with NSCLC

Objective: We aimed to explore what impact miR-503 has on the prognosis of patients with non-small cell lung cancer (NSCLC). Methods: Cancer and matched non-malignant lung tissue specimens were collected from 109 patients who underwent surgery in Tanisha Hospital from Jun 2006 to July 2013. Overall survival (OS) curves were analyzed using the Lapland-Meier method, and the differences were examined using log-rank tests. Cox proportional- hazards regression analysis was applied in order to estimate univariate and multivariate hazard ratios for OS. Results: The relative expression of miR-503 in NSCLC tissues (0.366 ± 0.130) was significantly lower than that in matched noncancerous lung tissues (1.667 ± 1.047, P < 0.01). Statistically significant association was observed between miR-503 expression and lymphatic invasion (P = 0.005), distant metastasis (P = 0.002), TNM stage (P = 0.008), and tumor grade (P = 0.043). Lapland Meier analysis clearly illustrated that the patients with the lower expression of miR-503 had a worse outcome compared to patients with higher miR-503 expression (P = 0.004). Furthermore, multivariate analysis revealed that miR-503 expression level was an independent prognostic factor for overall survival (HR = 3.992, 95% CI: 2.276-9.872; P = 0.018) in NSCLC. Conclusion: In patients with NSCLC, low miR-503 expression is an independent prognostic factor.     

Up-regulation of long non-coding RNA CCAT2 correlates with tumor metastasis and poor prognosis in cervical squamous cell cancer patients

Background: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. The purpose of this study was to investigate the relationship between lncRNA CCAT2 expression and cervical squamous cell cancer susceptibility and prognosis. Methods: Expression levels of lncRNA CCAT2 in 123 cervical squamous cell tumor specimens were determined by quantitative real-time PCR (qRT-PCR), to clarify the clinical significance of lncRNA CCAT2 in cervical squamous cell cancer, we further discussed the relationship between lncRNA CCAT2 expression and overall survival (OS) and progression-free survival (PFS). Results: In the present study, we found that lncRNA CCAT2 was up-regulated in cervical squamous cell cancer tissues compared to the adjacent non-tumor tissues. In addition, the high lncRNA CCAT2 expression was significantly associated with the FIGO stage, lymph node metastasis and depth of cervical invasion (P<0.05). Furthermore, patients with high expression of lncRNA CCAT2 had poor OS (HR=2.813, 95% CI: 1.504-6.172; P=0.017), and PFS rates (HR=3.072, 95% CI: 1.716-8.174; P=0.008). Multivariate Cox proportional hazard model analysis demonstrated that high lncRNA CCAT2 expression was an independent poor prognostic factor for cervical squamous cell cancer patients. Conclusions: Our study suggested that high expression of lncRNA CCAT2 is related to the prognosis of cervical squamous cell cancer; it may be a new prognostic biomarker and potential therapeutic target for cervical squamous cell cancer intervention.     

Upregulation of microRNA-23a/b promotes tumor progression and confers poor prognosis in patients with gastric cancer

Background and purpose: To investigate the clinical significance of microRNA (miR)-23a and miR-23b expression in human gastric cancer (GC). Methods: Quantitative RT-PCR was performed to detect the expression changes of miR-23a and miR-23b in 160 human GC tissues and paired normal mucosa. The associations between miR-23a and miR-23b expression, and the selected clinicopathological characteristics and patients’ prognosis were also evaluated. Results: MiR-23a (GC vs. Normal: 3.98 ± 1.23 vs. 2.29 ± 1.12, P < 0.001) and miR-23b (GC vs. Normal: 3.70 ± 1.24 vs. 1.58 ± 1.18, P < 0.001) expression were both increased dramatically when compared with paired normal mucosa. Notably, the expression levels of miR-23a in GC tissues were positively correlated with those of miR-23b (Spearman correlation coefficient r = 0.77, P < 0.001). Then, the coexpression of miR-23a and miR-23b (miR-23a-high/miR-23b-high) in GC tissues was significantly associated with the advanced TNM stage (P < 0.001), the presence of lymph node metastasis (P = 0.008) and the great depth of invasion (P = 0.02). Furthermore, both univariate and multivariate analyses showed that miR-23a/miR-23b co-expression was an independent predictor for unfavorable overall survival. Conclusions: These results suggest that the dysregulation of miR-23a and miR-23b may be implicated in the progression of human GC. Combined expression of miR-23a and miR-23b appears to be a valuable marker for prognosis of this disease.     

Decreased expression of microRNA-20a promotes tumor progression and predicts poor prognosis of cutaneous squamous cell carcinoma

Background: MicroRNA-20a (miRNA-20a or miR-20a) plays a key role in tumorigenesis and progression. But the prognostic value of miR-20a in cutaneous squamous cell carcinoma (CSCC) remains unclear. The aim of this study was to identify the association of miR-20a and the prognosis of CSCC patients. Methods: The miR-20a expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR) in 152 CSCC tissues and matched adjacent normal tissues. Kaplan-Meier and Cox regression analysis were utilized to determine the association of miR-20a with overall survival as well as the prognosis of CSCC patients. Results: The expression of miR-20a was lower in CSCC tissues compared with adjacent normal tissues (P=0.000). Moreover, the expression of miR-20a was closely correlated with TNM stage (P=0.013). Kaplan-Meier analysis showed that patients with low miR-20a expression had significantly poorer overall survival than those with high miR-20a expression (P<0.05). Multivariate analysis revealed that miR-20a expression (P=0.001, HR=3.262, 95% CI: 1.635-6.520) could influence the prognosis and might be an independent prognostic predictor in CSCC. Conclusions: Our results indicated that low miR-20a expression was associated with tumor stage of CSCC and suggested that miR-20a expression would be a novel biomarker for predicting clinical outcomes in CSCC patients. The inhibition of miR-20a might even become a new therapeutic method for the treatment of CSCC.     

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors

Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors.Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors.Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 - 0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 - 0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 - 0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer.Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.     

Increased expression of microRNA-150 is associated with poor prognosis in non-small cell lung cancer

Objectives: The aim was to evaluate the clinical significance and prognostic value of tissue miR-150 expression in non-small cell lung cancer (NSCLC) patients. Materials and methods: Quantitative real-time PCR was used to analyze the expression of miR-150. Overall survival (OS) was estimated using the Kaplan-Meier method, and the differences in survival were compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Results: Mean miR-150 levels were significantly higher in NSCLC tissues compared with matched non-cancerous tissues (4.07 ± 2.33 vs. 1.00 ± 0.46, P < 0.0001). The level of miR-150 in NSCLC was strongly correlated with lymph node metastasis (P = 0.04), distant metastasis (P = 0.01) and clinical TNM stage (P = 0.02). Kaplan-Meier analysis showed that the cumulative 5-year OS rate was 40.8% in the high expression group, and 69.2% in the low expression group. The log-rank test showed that the OS rate of patients with high miR-150 expression was significantly poorer than that of the remaining cases (P = 0.007). Conclusion: Our data indicated that overexpression of miR-150 in NSCLC tissues has prognostic value.